| 1. |
- Fan, Chuan-Wen, et al.
(författare)
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Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
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| 2. |
- Maddali, Manoj V., et al.
(författare)
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Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data : an observational, multicohort, retrospective analysis
- 2022
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600. ; 10:4, s. 367-377
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Tidskriftsartikel (refereegranskat)abstract
- Background: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine.
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| 3. |
- Zhang, Daquan, et al.
(författare)
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Large-scale planar and spherical light-emitting diodes based on arrays of perovskite quantum wires
- 2022
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 16:4, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- Halide perovskites are enticing candidates for highly efficient planar light-emitting diodes (LEDs) with commercial potential in displays and lighting. However, it remains a challenge for conventional solution fabrication processes to fabricate large-scale or non-planar LEDs due to the non-uniformity of perovskite films in conjunction with material stability issues. Here large-area highly uniform arrays of crystalline perovskite quantum wires are grown with emission spectra covering the whole visible range. Photoluminescence quantum yield of up to 92% and 5,644 hours as the time for photoluminescence to degrade down to its 50% of the initial value under ambient conditions are achieved for MAPbBr3 quantum wires. LEDs based on these quantum wires on rigid and flexible planar substrates are fabricated up to a four-inch wafer size and also unique three-dimensional spherical LEDs with outstanding uniformity are reported. The results suggest that the approach developed here can be generalized to other unconventional three-dimensional LEDs in the future.
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| 4. |
- Zhang, Xiao-Jie, et al.
(författare)
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Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation
- 2024
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Ingår i: Nature Structural & Molecular Biology. - : NATURE PORTFOLIO. - 1545-9993 .- 1545-9985. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development. Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.
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| 5. |
- Cheng, Jie, et al.
(författare)
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Interactions in Composite Film Formation of Mefp-1/graphene on Carbon Steel
- 2021
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Ingår i: Coatings. - : MDPI AG. - 2079-6412. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Mefp-1 adhesive protein derived from marine blue mussels, together with the 2D material graphene, was used to build the green composite film with enhanced anti-corrosion property and mechanical strength. The corrosion inhibition of the composite film, formed by different methods, was evaluated by using electrochemical impedance spectroscopy. The non-degraded adhesion of the composite film to the carbon steel substrate was proved by nano-scratch tests. Infrared spectroscopy was utilized to investigate the film formation process and "three-body interactions " between Mefp-1, graphene and carbon steel surface. The results show that the Mefp-1 adsorbs on the carbon steel surface mainly through the covalent bond between catechols and Fe(III). Meanwhile, Mefp-1 can bond to non-adhesive graphene by forming hydrogen bonds and pi-pi interaction non-covalent bonds, which facilitate the formation of a robust Mefp-1/graphene composite film on the carbon steel surface.
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| 6. |
- Deng, Bin, et al.
(författare)
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Modelling asymmetric deformation along a curved strike-slip basement-fault system
- 2021
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Ingår i: International journal of earth sciences. - : Springer. - 1437-3254 .- 1437-3262. ; 110, s. 165-182
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale curved strike-slip fault systems along which significant amounts of displacement have taken place are common in nature. Scaled analogue experiments were used in this study to investigate strike-slip deformation in cover units above a curved basement-fault system simulated by a rigid plate with an in-built curvature depicting a half-circular fault. The model results show that en-echelon, right-stepping Riedel shears and low-angle synthetic shears (Y-shears) always form at the beginning of deformation, and grow outwards with splay faults, most of which evolve into thrusts at later stages of deformation. Digital image correlation (DIC) analyses of the surface displacement vectors show that a diffuse zone of deformation progressively changes into en-echelon shears, which gradually develop into throughgoing shear zones with further deformation. The geometries of Riedel shears along two sides of the basement fault (i.e. concave and convex sides) show significant differences in fault shape and intersection angles between the faults and the curved basement fault, indicating an asymmetry in deformation with a much wider deformation zone occurring on the concave side. As a result, en-echelon and/or overlapping flower structures develop along the curved basement strike-slip fault system. In particular, Riedel shears with a upward-convex geometry are localised in both sides of the curved basement fault and a continuous reverse oblique-slip fault forms at the concave side. When compared with the geometry of curved strike-slip faults in nature (e.g. the Daliangshan shear zone in Xichang basin and the Red River shear zone in the Yinggehai basin, China) the model results depict the asymmetric evolution pattern of the faults on either side of curved basement faults.
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| 7. |
- Fan, Dongming, et al.
(författare)
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Robustness of maintenance support service networks : attributes, evaluation and improvement
- 2021
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Ingår i: Reliability Engineering & System Safety. - : Elsevier. - 0951-8320 .- 1879-0836. ; 210
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Tidskriftsartikel (refereegranskat)abstract
- Maintenance support service network (MSSN) is used to provide maintenance services and maintain the operational status of equipment. However, the performance of MSSN has been significantly influenced by inevitable disturbance, which makes it vital to maintain its robustness. Existing research on robustness of MSSN mainly focuses on single-layer rather than two-layer network, which imposes constraints on the disturbances and limits its application. To solve these issues, this study develops a two-layer MSSN, consisting of a directed entity-layer and an undirected cyber-layer focusing on supporting maintenance service. A definition of robustness for two-layer MSSN is proposed, and effect propagation models are established to evaluate its robustness of MSSN, followed by its improvement strategies. In particular, two strategies applied in the single-layer MSSN are modified to adapt to the two-layer MSSN, and a novel greedy partnership building approach is proposed to find an optimal strategy under cascading failure, to maintain the robustness of MSSN from a complex network perspective. Finally, numerical examples are presented to illustrate the effectiveness of the proposed approach.
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| 8. |
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| 9. |
- Fan, Zhirui, et al.
(författare)
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Multiscale eigenfrequency optimization of multimaterial lattice structures based on the asymptotic homogenization method
- 2020
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Ingår i: Structural and Multidisciplinary Optimization. - : Springer Science and Business Media LLC. - 1615-147X .- 1615-1488. ; 61:3, s. 983-998
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Tidskriftsartikel (refereegranskat)abstract
- Ultralight lattice structures exhibit excellent mechanical performance and have been used widely. In structural design, the fundamental frequency is highly important. Therefore, a multiscale topology optimization method was utilized to optimize the fundamental frequency of multimaterial lattice structures in this study. Two types of optimization problems were studied, namely, maximizing the natural fundamental frequency with mass constraints and minimizing compliance with frequency constraints. The Heaviside-penalty-based discrete material optimization method was adopted for the optimal selection of candidate materials. The asymptotic homogenization method was used to evaluate the equivalent macroscale properties according to the microstructure of the lattice material. To enable gradient optimization, sensitivities were outlined in detail. A density filter with a volume-preserving Heaviside projection was used to eliminate the risk of a checkerboard pattern and reduce the number of gray elements. A polynomial penalization scheme was employed to eliminate localized spurious eigenmodes in the low-density region. Finally, several numerical examples were performed to validate the proposed method. These numerical examples resulted in novel microstructural configurations with remarkably improved vibration resistance.
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| 10. |
- Fan, Zhirui, et al.
(författare)
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Nonlinear stiffness optimization with prescribed deformed geometry and loads
- 2022
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Ingår i: Structural and Multidisciplinary Optimization. - : Springer Science and Business Media LLC. - 1615-147X .- 1615-1488. ; 65:2
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Tidskriftsartikel (refereegranskat)abstract
- Optimization based on traditional forward motion analysis to ensure a prescribed load distribution on a deformed geometry is challenging, since the load distribution is highly coupled to the deformed geometry, boundary conditions, and the optimized material layout. In contrast to traditional forward motion analysis, the deformed configuration is prescribed in the inverse motion analysis, and the undeformed configuration is the outcome of the analysis. Consequently, the inverse motion analysis is able to define an exact deformed geometry. In the present study, we make use of this key advantage to design structures with both an exact deformed geometry and a prescribed load distribution. The objective in the optimization is to minimize a general function of the nodal displacement vector. To formulate a well-posed optimization problem, the design is regularized using the partial differential equation filter and the sensitivity analysis is based on the adjoint method. The computational model is developed for neo-Hookean hyper-elasticity and the balance equations are discretized using the finite element method. The resulting nonlinear equations are solved using a conventional Newton–Raphson scheme. In the numerical examples, a cantilever beam with an embedded perfect circular shape is first considered. Next, a 2D gasket-like structure is designed, and finally, we consider a 3D structure with contact-like boundary conditions. In these examples, the prescribed deformed geometry is subject to a distributed external force. The examples show that the deformed geometry and load distribution can be exactly prescribed through stiffness optimization based on the inverse motion analysis.
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